Abstract
<jats:p>DNA-stabilized silver nanoclusters (DNA-AgNCs) have attracted significant attention due to their tunable fluorescence, biocompatibility, and potential applications in sensing and nanophotonics. Despite significant experimental progress on deciphering the structural details, the molecular level understanding of DNA-AgNC systems remains elusive and due to the challenges associated with reaching spatio-temporal resolution. Computational studies, in particular, molecular dynamics simulations would unveil such microscopic and dynamic details, however, due to the lack of good potential models for DNA-AgNC systems, such methods, to the best of our knowledge, have never been used. Here, we report one of the first classical MD studies of DNA-stabilized silver nanoclusters. By benchmarking different charge models and the interaction parameter sets, we propose a robust MD simulation protocol capable of simulating a DNA-AgNC in water over extended simulation timescales. These simulations reveal features of AgNC stabilization and its structural dynamics within the DNA environment. Furthermore, enhanced sampling simulations uncover the free-energy landscape and atomistic mechanism of silver atom exchange between two DNA-AgNC moieties, revealing thermally accessible barriers (∼50–100 kJ/mol) that connect nearly isoenergetic native (16/16) and exchanged (15/17) occupancy states, consistent with experimentally observed exchange timescales. The Ag-exchange proceeds through transient, partially desolvated intermediates while preserving both metallic-core geometry and DNA-scaffold integrity. These results provide the first atomistic mechanism for reversible metal exchange between DNA-AgNCs, offering a computational foundation for understanding the dynamic stability of this emerging class of bio-nanomaterials.</jats:p>